1. Field of the Invention
The present invention relates to methods and compositions for identifying and detecting lethal cell useful for monitoring disease status and therapy responses in various types of cancer patients regardless of the etiological origin of the cancer and uses thereof.
2. Prior Art
Although Hanahan and Weinberg in 2000 (Cell, 2000, 100:57-70) had enumerated the hallmarks of cancer, the currently-developed therapies based on this concept with major focus on the aggressive behavior of conventional cancer cells often failed to cure the cancer patients during the last 50 years. The recent studies have challenged that on some occasions, the incurable tumors, cancer cells and markers are merely the end products of the disease. There is increasing evidence that bone marrow-derived stem/progenitor cells (BMDSC) can be disseminated throughout the body and continually recruited in a variety of situations to the stroma of developing tumors closely resembling overhealing wounds which entail the constant deposition of growth factors, chemokines, cytokines and tissue-remodeling factors that can gradually destroy the organ microenvironments resulting in organ failures and simultaneously pave the milestones to facilitate host-immunosuppression, anti-apoptosis, malignant transformation of epithelia, proliferation, growth, invasion, and metastatic spread of cancer cells. However, the controversial and paradoxical roles of BMDSC comprising various types of stem/progenitor cells and derivatives such as fibroblasts and macrophages in incurable cancer development and progression remain a great challenge to solve the current cancer problems (Bingle et al, J Pathol, 2002, 196:254-265; De Wever and Mareel, J Pathol, 2003, 200:429-447; Condeelis and Pollard, Cell, 2006, 124:263-266; Direkze and Alison, Hematol Oncol, 2006, 24:189-195; Kaplan et al, Trends Mol Med, 2007, 13:72-81; Karnoub et al, Nature, 2007, 449:557-563; Loberg et al, CA Cancer J Clin, 2007, 57:225-241; Massberg et al, Cell, 2007, 131:994-1008; Biswas et al, J Immunol, 2008, 180:2011-2017; Chantrain et al, Cancer Microenviron, 2008, 1:23-35; Germano et al, Cytokine, 2008, 43:374-379; Laird et al, Cell, 2008, 132:612-630; Le Bitoux and Stamenkovic, Histochem Cell Biol, 2008, 130:1079-1090; Takaishi et al, J Clin Oncol, 2008, 26:2876-2882; Aggarwal and Gehlot, Curr Opin Pharmacol, 2009, 9:1-19; Gonda et al, Cell Cycle, 2009, 8:2005-2013; Joyce and Pollard, Nat Rev Cancer, 2009, 9:239-252; Mishra et al, Cancer Res, 2009, 69:1255-1258; Psaila and Lyden, Nat Rev Cancer, 2009, 9:285-293). It has been challenged that besides the traditional molecular oncology study with major focus on conventional cancer cells during the last 50 years, the cellular and clinical oncology studies and more particularly the systemic oncology study should be simultaneously emphasized.
Proline-directed protein kinase FA (PDPK FA)/glycogen synthase kinase-3α (GSK-3α) was originally identified as a specific protein phosphatase activating factor A (Vandenheede et al, J Biol Chem, 1980, 255:11768-11774; Yang et al, J Biol Chem, 1980, 255:11759-11767; Woodgett, EMBO J, 1990, 9:2431-2438). In this lab, PDPK FA/GSK-3α was further characterized as a multisubstrate/multifunctional PDPK associated with anti-apoptosis, anti-differentiation, tumorigenesis, invasion and chemoresistance of various types of conventional cancer cells (Lee et al, J Cell Biochem, 1995, 58:474-480; Yang et al, J Cell Biochem, 1995, 59:143-150; Yang et al, J Cell Biochem, 1996, 61:238-245; Hsu et al, Br J Cancer, 2000, 82:1480-1484; Hsu et al, Cancer, 2000, 89:1004-1011; Yang et al, Clin Cancer Res, 2000, 6:1024-1030; Hsu et al, Cancer, 2001, 92:1753-1758; Hsu et al, Int J Cancer, 2001, 91:650-653; Chung et al, Cancer, 2002, 95:1840-1847; Hsueh et al, Cancer, 2002, 95:775-783; Fu and Yang, Anticancer Res, 2004, 24:1489-1494; Yang, Curr Cancer Drug Targets, 2004, 4:591-596; Yang, Drug News Perspect, 2005, 18:432-436; Hsu et al, J Clin Oncol, 2006, 24:3780-3788). Unfortunately, the previous work on PDPK FA/GSK-3α was mainly associated with the current mainstream cancer research with major focus on conventional cancer or precancer cells as described above. The impact of this signal transducing molecule in cancer therefore remains to be evaluated.